Tecan Journal Edition 03/2015

TJ Edition 3/2015

Tecan Journal

Life Sciences and Diagnostics

A new kind of biobanking pages 14 - 15

A personal touch for wine microbiology pages 22 - 23

Human genetics – mapping the future of medicine pages 26 - 27

Fingerprinting food pages 16 - 17

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Welcome to the Tecan Journal

In this issue, we look at the increasing role of automated sample preparation in genomics. As ever-falling sequencing costs mean more and more laboratories begin to take advantage of the latest sequencing technologies, walkaway processing and analysis is the key to reducing the cost of testing.

Renowned molecular diagnostics specialist Dr Pierre-Alain Menoud shares his insights on this topic (pages 26-27), looking at the future of genomics in the healthcare environment.

The clinical community had a chance to explore this trend further at the AACC Annual Meeting and Clinical Lab Expo in July, where Tecan showcased a number of application-oriented Freedom EVOŽ platforms and some exciting updates for the Fluent™ laboratory automation solution. Designed to simplify key processes and increase productivity, these latest offerings are ideally suited to high throughput genomics applications. This event also played host to the latest Tecan Symposium, which focused on recent developments in immunodiagnostics, providing a friendly, informal atmosphere to discuss the benefits and challenges new technologies bring.

You can read more about these events and our recently launched products in this issue, along with a number of other stories looking at how Tecan instruments are helping to streamline the clinical environment for both routine testing and research.

I hope you enjoy this issue, David Martyr, CEO

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page 8

A new air displacement Flexible Channel Arm means that Fluent now offers the choice between two pipetting technologies

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CEO Welcome

4 - 5

Tecan @ AACC 2015

6 Walkaway batch processing for the Spark™ 10M pages 10 - 11

6 Tecan’s D300e offers fast liquid transfer down to picoliter levels 7 Novel ELISA offers improved diagnosis for myasthenia gravis 7 Explore virtual components with the new Tecan Cavro® app 8 Fluent takes precision and accuracy in liquid handling to the next level 9 Cavro ADP a hit with Chinese in vitro diagnostic customers 10 - 11 Automation helps enhance diagnostics protocols 12 - 13 Automating the development of aptamer-based biological tools

pages 24 - 25

14 - 15

A new kind of biobanking

16 - 17

Fingerprinting food

18 - 19 Off-the-shelf NGS library prep for Ion Torrent™ sequencing 20 - 21

Designer proteins

22 -23 A personal touch for wine microbiology 24 - 25 Accelerating results from bench to bedside 26 - 27 Human genetics – mapping the future of medicine pages 26 - 27

The ever-increasing demand for testing means that sample numbers will continue to rise steadily for molecular diagnostics laboratories

28 Events

CONTENTS TECAN JOURNAL 3/2015

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Tecan @ AACC 2015 The clinical community enjoyed another successful AACC exhibition, giving delegates from around the world the opportunity to learn about the latest developments for clinical research and diagnostics.

The AACC Annual Meeting and Clinical Lab Expo is a highlight of the clinical chemistry calendar, bringing together key opinion leaders, equipment manufacturers and diagnostic kit providers from around the world. Tecan had a strong presence at this year’s event – held in Atlanta, Georgia – showcasing a range of automation solutions for two of the current hot topics in diagnostics: the increasing role of automated sample preparation in genomics, and the latest developments in the field of immunodiagnostics.

With the ever-increasing role of genomics and personalized medicine in patient care (read more about this topic on pages 26-27), reliable and reproducible sample preparation is now vital. Tecan demonstrated a wide range of automation technologies for this application – including the turnkey Freedom EVO® NGS workstation and the Fluent™ laboratory automation solution – generating a lot of interest among the meeting’s 18,000 attendees. Visitors also had the opportunity to explore the OEM capabilities of Tecan’s Partnering Business, including the first public demonstration of the company’s advanced eFluidics electrowetting technology and the use of Tecan Cavro® brand components in DaAn Gene’s DA3000 DNA extraction system (read about this system on page 9).

This year also saw IBL International join Tecan for the first time. Perfectly complementing Tecan’s existing offerings for the clinical immunodiagnostics market, the IBL International team was able to provide visitors with an insight into the latest innovations in immunodiagnostics, as well as the benefits of combining microplate-based diagnostics with efficient automated liquid handling workstations – such as the Freedom EVOlyzer® and Freedom EVO ELISA platforms – to streamline laboratory workflows. Tecan was also pleased to be able to contribute to the AACC Biomarkers of

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Cardiovascular Disease Division’s project to establish 99th percentile values for the latest generation of high sensitivity troponin assays.

Aiming to collect samples from 1,100 volunteers across the five days of the event, samples gathered by a team of phlebotomists in the exhibition hall were processed for cryostorage

in a pop-up lab. This sample collection is now with the United States Centers for Disease Control and Prevention, and will be made available to diagnostics companies offering high sensitivity troponin assays, helping to establish relevant cut-offs and improve diagnostic accuracy.

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Symposium 2015 Alongside the main AACC conference and exhibition, Tecan invited a number of leading academics and industry figures to attend the latest Tecan Symposium – New frontiers in immunodiagnostics. After a two year absence, the return of this highly regarded event gave delegates from across the clinical sector the opportunity to discuss the latest technical developments and unmet needs in immunodiagnostics in a relaxed, informal atmosphere.

Following a welcome from Dr Achim von Leoprechting, Executive Vice President of Tecan’s Partnering Business, and Dr Mike Martens, Managing Director of Future Diagnostics – a key strategic partner for Tecan – the program for the symposium was introduced by Tecan’s Nicholas Smith, Head of Global Marketing and Portfolio Management, and included presentations from a number of the industry’s key opinion leaders.

Dr Peter Schulz-Knappe, CSO of Protagen AG, opened proceedings with a presentation entitled From “omics“ biomarker discovery to novel clinical tests: strategies and challenges, providing an insight into the various approaches and pitfalls in the selection of new markers and development of novel clinical assays. This was followed by Biotherapeutic drug and immunogenicity monitoring, a critical look at the role of companion diagnostics from Dr Kelly Y Chun, VP and Director at Laboratory Corporation of America.

Using infliximab – a chimeric monoclonal antibody for the treatment of Crohn's disease – as an example, Dr Chun discussed the need for greater clinician education to avoid potential misinterpretation of results and ensure the best outcomes for patients.

Point of care immunoassays: challenges and platform implications was the topic chosen by Dr Jeroen Nieuwenhuis, Technology Director of the Philips Healthcare Incubator. He discussed how the ever-increasing role of point of care and near patient testing is affecting the way healthcare services are delivered, highlighting the potential of robust, reliable technologies – such as microfluidics – in enabling a more

personalized approach to patient care. The final speaker – Dr Jeffrey Bishop, Vice President of Research and Development at Singulex – looked at The impact of ultra-sensitivity immunoassays: a change in diagnostic modalities. Using the advent of high-sensitivity troponin assays as an example, he discussed how clinician education is becoming increasingly important for the effective use of these assays for both diagnostic and prognostic applications.

The interactive presentations were followed by a panel discussion with the speakers, giving members of the audience a chance to pose specific questions and look at the various topics in more detail. This enlightening event was followed by a meal at internationally-renowned broadcaster CNN’s headquarters, with a tour of the CNN tower facility providing a unique opportunity to continue the discussion and explore exciting new opportunities over a glass or two.

To find out more about upcoming Tecan events, go to www.tecan.com/events

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Walkaway batch processing for the Spark™ 10M The Spark 10M multimode reader can now be combined with the Connect™ microplate stacker to offer semi-automated batch processing of up to 50 assay plates. A newly developed software interface allows seamless operation of the Connect stacker through the reader’s SparkControl™ software, helping to streamline your laboratory workflow for greater productivity.

The Connect is a versatile microplate stacker designed to offer fast, smooth transfer of plates to and from the host instrument.

Already popular with customers using Infinite® series readers and HydroSpeed™ plate washers, this proven and reliable system can now be used in conjunction with the powerful Spark 10M reader. All common microplates conforming to ANSI/ SLAS standards – from 6- to 1,536-wells – can be used with Connect, with a choice of

The Connect stacker offers walkaway processing for up to 50 microplates using the Spark 10M

30- or 50-plate cassettes to suit a variety of throughputs. Optional dark covers are also available to protect light sensitive reactions, making the system ideally suited to a wide range of applications in genomics, proteomics and drug discovery.

To find out more about Tecan’s Connect stacker and Spark 10M multimode reader, visit www.tecan.com/connect and www.tecan.com/spark

Tecan’s D300e offers fast liquid transfer down to picoliter levels Tecan has introduced the D300e Digital Dispenser* for applications that need faster, reliable dispensing down to picoliter volumes.

This innovative, simple-to-use device is ideal for the creation of assay plates, and can cut set up times from hours or days to just minutes.

Users can choose between dispensing aqueous solutions in combination with a surfactant – for the investigation of proteins, antibodies, enzymes and nucleic acids – and DMSO, for small molecule studies, offering greater flexibility for life sciences workflows.

The system’s sophisticated yet easy-to-use software guides you through every operation, minimizing training times and problem-solving call-outs, and providing straightforward set up of enzyme profiles, dose-response curves and synergy studies. Even the most complex experimental plate layouts – such as drug-drug interaction studies – can be quickly and easily generated, with optional randomization to

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reduce the impact of edge effects and increase data integrity. The D300e is compatible with a wide range of microplate formats from 12 to 1,536 wells, including deep-well plates and, for maximum flexibility, can even accommodate ANSI/SLAS-format tube racks.

To find out more about Tecan’s D300e Digital Dispenser, visit www.tecan.com/D300e * For research use only. Not for use in diagnostic procedures.

Tecan’s D300e Digital Dispenser

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Novel ELISA offers improved diagnosis for myasthenia gravis IBL International’s MuSk-Ab ELISA is proving invaluable for the diagnosis and monitoring of ‘seronegative’ myasthenia gravis (MG).

This test is the world’s first commercially available, non-radioactive assay for the detection of auto-antibodies against the muscle-specific receptor tyrosine kinase (MuSK), and is helping to improve diagnostic confidence and aid clinical management of these patients.

MG is an antibody-mediated autoimmune disease of the neuromuscular junction, and can be readily diagnosed in 80 % of patients through the presence of acetylcholine receptor antibodies (ARAbs). However, this biomarker is not present in around 20 % of patients, making diagnosis of these ‘seronegative’ patients complex. To overcome this issue, IBL International has created a quantitative ELISA which targets the characteristic MuSK auto-antibodies present in MG. This straightforward, reproducible and easy-to-automate assay offers exceptional

diagnostic performance – with almost 100 % clinical sensitivity and selectivity – allowing rapid, clear diagnoses for this patient subpopulation. The excellent performance of this assay also enables therapeutic monitoring of patients, exploiting the correlation between MuSK-Ab levels and disease severity1 to allow ongoing clinical assessment. Combined with IBL’s ARAb radioimmunoassays, the MuSk-Ab ELISA provides a comprehensive solution for the diagnosis of MG.

To find out more about IBL’s MuSK-Ab ELISA, visit www.ibl-international.com/en/muskab-elisa 1) Damoiseaux, J et al. Detection of anti-MuSK antibodies by a novel quantitative ELISA. Presented at the 9th International Congress on Autoimmunity, 2014, 26-30 March, Nice, France.

Explore virtual components with the new Tecan Cavro® app Customers can now explore the Tecan Cavro range of liquid handling components on the go, with the launch of the Tecan Cavro Components app. This straightforward, web-based application – available for PCs or iPads® – combines the existing Cavro Omni Robot Configurator with interactive 3D models of key products from the Tecan Cavro range.

functions and liquid handling configurations – as well as a number of finishing features, such as covers and end caps. Users can generate 3D representations of their desired Cavro Omni Robot specification, providing visual confirmation of how the selected configuration will fit, as well as quick and easy verification of the dimensions that might affect instrument design.

The Cavro Omni Robot Configurator allows systems developers to create over 100 different designs of this flexible liquid handling robot, making it easy to visualize and plan instrument designs for faster product development. It provides details of the complete range of standard options for the Cavro Omni Robot – including the various axis sizes and arrangements, arm

The new app also offers interactive 3D models of other products from the Tecan Cavro range – including the Centris, XCalibur, XE 1000 and XLP 6000 pumps, as well as the ADP pipettor module – which can be rotated on the screen to help visualize each component from different perspectives. Each model also provides details of key product features, as well as allowing the user to

request more information from their local Tecan representative, helping to simplify and accelerate product development.

To download the Tecan Cavro Components app, go to www.tecan.com/components

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Fluent™ takes precision and accuracy in liquid handling to the next level The flexibility of the Fluent laboratory automation solution* has been enhanced with the launch of a number of new hardware and software options designed to enable a much wider range of applications. These updates build on the success of the Fluent cell-based assay and compound management workstations, further simplifying key processes and increasing productivity in the lab, as well as being ideally suited to high throughput genomics applications.

A new air displacement Flexible Channel Arm means that Fluent now offers the choice between two pipetting technologies for high definition liquid handling, unmatched precision and greater accuracy. This is complemented by a revolutionary new Active Stop and Resume function, which uniquely allows operators to access and interact with the workdeck during a run, simply by opening the door. To restart, the user just closes the door and reinitiates

the program, which will pick up where it left off. Process security has also been enhanced with the option of a mobile barcode scanner mounted on the platform’s Robotic Gripper Arm, allowing labware IDs to be confirmed as they are moved around the worktable, or ‘inventory’ scans of plate hotels prior to beginning a run to ensure all samples are accounted for.

The workstation’s FluentControl™ software has been further enhanced with the addition of an Application Toolkit providing standard commands for common tasks, such as quantification and normalization workflows.

These new command sets have been developed to simplify programming for both application specialists and less experienced users, saving several hours per script compared to current solutions on the market.

It also provides a collection of commands allowing programmers to create ‘wizard-like’ interfaces, with special

The Fluent laboratory automation solution can now be used for a far wider range of applications

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commands for embedding rich user prompts.

Combined with existing Smart Commands and an ever-increasing library of third-party device drivers – including support for SiLA devices – this toolkit offers faster process development while simplifying everyday operation and technical support.

“We are particularly proud of how the Fluent platform has been received by early users, with some customers already coming back to order additional systems. This new wave of innovation takes our central concepts of userfriendliness and ease of use to the next level for laboratory automation,” commented Dr Stefan Traeger, Executive VP and Head of the Tecan Life Sciences Business.

To find out more about Tecan’s Fluent workstations, visit www.tecan.com/fluent * For research use only. Not for use in diagnostic procedures.

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Cavro® ADP a hit with Chinese in vitro diagnostic customers Chinese company DaAn Gene has integrated the Cavro Air Displacement Pipettor (ADP) into its new generation of molecular diagnostic instruments, bringing the advantages of Tecan’s liquid pipetting expertise to blood banks and infectious disease laboratories in China.

into instruments, giving exceptional liquid handling performance from 1-1,000 µl. It uses air displacement to aspirate and dispense fluids, requiring minimal maintenance, and correct operation is monitored by on-board, DaAn Gene is a major supplier to the Chinese in vitro diagnostics (IVD) market, specializing in molecular diagnostic kits and reagents for more than 20 years. In 2005, the company began to design and manufacture instrumentation to support its reagent business and, in 2009, chose to incorporate Tecan Cavro components into its DA3000 DNA extraction system for infectious disease screening in blood banks.

Mr Junan Hong, Research and Development Director for DaAn Gene, explained: “The Tecan name is already well known in hospital laboratories in China, where the Freedom EVO® series is used extensively for liquid handling and sample preparation applications. Tecan Cavro components are renowned for offering high reliability and high performance, and it made sense for us to choose the Cavro ADP pipetting solution and Cavro XLP syringe pump for

pressure-based liquid level detection. A builtin tip sensor checks if a disposable tip has not been correctly picked up, or has fallen off the probe, flagging and logging errors to increase process security. The DA3000 is unique in that it features four ADP modules running in parallel, dramatically increasing the throughput of the instrument and resulting in a very competitive product for DaAn Gene to release to the Chinese market.

The Cavro ADP is ideally suited to DaAn Gene’s needs, offering exceptional liquid handling performance and requiring minimal maintenance

throughput applications, we aim to produce similar options with fewer ADP modules for

Mr Hong continued: “We are very happy

low to medium throughput facilities.”

with the excellent product performance and quality, plus the strong support we

To learn more about DaAn Gene, go to

have received, both from the local Tecan

daan.joomcn.com

team in China and application specialists in the US. These components are the right

To find out more about the Tecan Cavro

products for this application in blood banks

range of OEM components, visit

and infectious disease control centers. We

www.tecan.com/components

are already developing other instruments to suit different workloads and, where the DA3000’s four ADP pipettors deal with high

our instruments.”

In the last year or so, Chinese laboratories have begun to turn to DNA extraction and PCR for infectious disease testing in blood banks, moving on from the more traditional ELISA techniques. Where most suppliers in the Chinese market use liquid displacement techniques in their liquid handling solutions, DaAn Gene is leading the way with the use of air displacement technology in the context of an IVD instrument. The Cavro ADP is a compact, fully programmable, pneumatic pipetting solution that is easy to integrate

Automation is crucial for high throughput blood banks

Cavro Air Displacement Pipettor

CLINICAL DIAGNOSTICS TECAN JOURNAL 3/2015

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Automation helps enhance diagnostics protocols The Molecular Biology Department at Colombia’s Laboratorio Clinico Medico Colcan is using a Freedom EVO® 150 liquid handling platform to automate its nucleic acid extraction and real-time PCR protocols, offering increased flexibility and helping to improve sample throughput.

Laboratorio Clinico Medico Colcan, a private laboratory in Bogotá, Colombia, provides a broad range of diagnostic services to clinical laboratories, hospitals, clinics and individual patients across the country. Tecan instruments feature across the laboratory, and include a Genesis FE500 for pre-analytical sample preparation, a Freedom EVOlyzer®, a Sunrise™ plate reader and a HydroFlex™ plate washer for ELISAs and, in the Molecular Biology Department, a Freedom EVO 150 for automated nucleic acid extraction and real-time PCR reactions. Scientific Advisory Specialist Mauro Rodríguez discussed the automation of the department’s molecular diagnostic procedures on the Freedom EVO 150: “We perform a variety of molecular diagnostic tests for different pathogens and conditions, including HIV, hepatitis B, human leukocyte antigen (HLA) B27, mycobacteria, herpes, HPV, CMV and mutation of the coagulation factors II and V genes. Currently, many of our sample preparation protocols are run on a commercially-available platform, which is a closed system. This means that the protocols cannot be modified, and the system can only run certain kits specified by the manufacturer; other assays must be performed manually. To enable automation

of all our molecular testing protocols, we invested in an open architecture Freedom EVO 150, giving us the flexibility to run a range of chemistries from different companies.”

Ignacio Hernández, Specialist, took up the story: “We use a range of Promega kits on our existing molecular diagnostic system, and these acted as controls for the Freedom EVO validation study. Extraction protocols for the different chemistries were run on both automated systems and the purity and concentration of the extracted nucleic acids compared. The Freedom EVO was also compared to our manual assays, ensuring that the automated procedures were as effective – or better – than these processes. This enabled us to develop and standardize automated procedures for the isolation of DNA on the Freedom EVO system. We now analyze around 350

samples a week on the Freedom EVO, isolating purer, more concentrated nucleic acid samples with fewer contaminants, helping to improve the quality of downstream amplification and analysis.

We have also automated our real-time PCR procedures, and plan to introduce a number of end-point PCR protocols.”

Ignacio continued: “Implementation of the Freedom EVO in our laboratory was fast and straightforward; the software is easy to use and it fits perfectly into our workflow. Its open architecture provides more flexibility for our work – we can modify the volume of samples, emulsions and reagents, as well as incubation times and other parameters affecting the concentration and purity of the isolated DNA – allowing us to optimize our protocols, which we cannot do on a closed system. For example, we perform

“We now analyze around 350 samples a week on the Freedom EVO, isolating purer, more concentrated nucleic acid samples with fewer contaminants.”

Mauro Rodriguez, Miguel Rios and Ignacio Hernández with the Freedom EVO platform

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HLA B27 analysis using a combination of PCR amplification and gel electrophoresis, which requires high concentrations of very pure genetic material. By doubling the initial sample volume, we can generate a much higher concentration of nucleic acids without affecting the purity, maximizing the likelihood of successful PCR and electrophoresis for better quality, more reliable results.”

Mauro concluded: “We chose the Freedom EVO for its quality, and because it could meet the laboratory’s needs in terms of speed of processing, sample throughput and performance. Another benefit is that the maintenance requirements are minimal. Automation enables samples to be aliquoted, contributing to improved sample set-up times, and the overall extraction procedure is much more rapid. It also helps to prevent manual errors occurring during the pre-analytical process, decrease the risk of contamination during extraction and, with the Freedom EVO’s PosID™ Positive Identification System, sample traceability and process security are guaranteed. The system is very user friendly and easy to program, offering infinite possibilities for our assays.”

A Genesis FE500 provides automated pre-analytical sample preparation

To find out more on Tecan’s genomics solutions, visit www.tecan.com/clinicaldiagnostics To find out more about Laboratorio Clinico Medico Colcan, visit www.laboratoriocolcan.co The Freedom EVO offers walkaway automation of nucleic acid extraction and real-time PCR protocols

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Automating the development of aptamer-based biological tools The Institut Européen de Chimie et Biologie is investigating a variety of innovative aptamer-based applications, and depends on two Freedom EVO® platforms for reliable automation of its selection and production processes.

The Institut Européen de Chimie et Biologie (IECB) in Bordeaux, France, is home to a number of interdisciplinary research teams operating under the joint authority of the National Center for Scientific Research (CNRS), the French National Institute of Health and Medical Research (Inserm) and the University of Bordeaux. IECB scientists in the ARNA Laboratory are working at the interface between molecular biology, molecular biophysics and chemistry, using aptamers to perform both fundamental and applied medical research. These single-stranded DNA or RNA oligonucleotides can bind to pre-selected targets – including proteins and peptides – with high affinity and specificity, providing opportunities for the development of novel tools for biological applications. To increase throughput, the ARNA Laboratory has automated

its procedures on two Freedom EVO platforms, as Inserm Research Director Dr Jean-Jacques Toulmé explained: “Our team focuses on the design, selection and characterization of aptamers for in-house projects – for example, artificial regulation of viral or prokaryotic gene expression – and the development of various aptamer-based tools for applications such as imaging tumors and the design of biosensors. In addition, we have a strong emphasis on technology transfer for practical applications, as well as providing aptamers for other academic groups or external companies from various industries for their own applications. We have been working in this field for almost 20 years now, pursuing both upstream fundamental research and the more applied technical development of practical applications.”

“The Freedom EVO is a great benefit, freeing up staff time and helping us to achieve the desired throughput.”

The laboratory’s Freedom EVO platform has a range of integrated devices to offer almost complete automation of its workflow

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The ARNA Laboratory team

Jean-Jacques continued: “Our association with Tecan and the implementation of the Freedom EVO workstations in our laboratory began around 10 years ago when we came across a paper describing an automated selection platform. We decided to automate our selection protocols to allow us to screen large libraries of oligonucleotides, and contacted various suppliers before choosing Tecan. After a lot of discussion with the company, we invested in a Freedom EVO platform with an integrated incubator, Te-VacS™ magnetic separator and PCR system, enabling the process to be almost completely automated. We generally perform two selections in parallel – either two different targets, or two different conditions for the same target – which is usually between 8 and 15 runs. With each run taking around six hours, the selection process is completed in about a week to 10 days. This would be a difficult and time-consuming process to do manually, and is a tedious, repetitive task for a scientist to carry out.

The Freedom EVO is a great benefit, freeing up staff time and helping us to achieve the desired throughput.”

natural to turn to Tecan. We discussed the best configuration for this new workstation and decided to incorporate a fluorescence detector, choosing the Infinite® M1000 PRO multimode reader. This gave us the capability to use additional techniques, including AlphaScreen® assays and fluorescence anisotropy, which was essential as we wanted to screen candidates by function, rather than the more commonly used affinity assays. Automation allows us to quickly and easily screen large numbers of different candidates against our targets.

We design our assays according to the function that we want to detect and, in contrast to the standard procedure where perhaps 100 candidates are sequenced, we blindly produce three 384-well plates containing hundreds of candidates. These candidates are then screened using the Infinite reader.

Fluorescence anisotropy is our preferred screening method, as it simply requires the use of a fluorescently-labeled target or oligonucleotide candidate, eliminating the need for magnetic beads and giving good reproducibility.”

“About five years ago, we realized that we needed a second automated platform for our production processes, and it was

The growing interest in aptamers has led to the creation of a technology transfer unit – Novaptech – to facilitate

commercial development of these molecular tools. Using the same Freedom EVO-based automated workflow as the ARNA Laboratory, Novaptech focuses on the identification and characterization of aptamers for analytical and diagnostic applications, performing both collaborative projects and screening services for academic laboratories and biotechnology companies around the world. Jean-Jacques concluded: “The Freedom EVO platforms and the Infinite reader are easy to operate, and we can do all the script programming in house. Our staff are really happy with the systems and the software. We have had some interesting contributions from Tecan, and everything is working very smoothly.”

To find out more about Tecan’s protein purification and characterization solutions, visit www.tecan.com/proteinscience To find out more about the Institut Européen de Chimie et Biologie, visit www.iecb.u-bordeaux.fr To find more about Novaptech’s services, visit www.novaptech.com

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A new kind of biobanking University Hospital Regensburg has taken advantage of the open architecture of the Freedom EVO® workstation, creating a seamless connection between its routine diagnostics and biobanking activities. Working in partnership with the hospital’s Institute for Laboratory Medicine and Transfusion Medicine and diagnostic instruments provider, the Tecan Integration Group has developed a bespoke solution which offers fully automated preparation of samples for both biobanking and offline secondary testing.

Professor Gerd Schmitz, formerly Director of the Institute for Laboratory Medicine and Transfusion Medicine at University Hospital Regensburg

The Institute for Laboratory Medicine and Transfusion Medicine at University Hospital Regensburg combines routine diagnostic testing with basic research, evidence-based medicine and clinical studies. In addition, the institute maintains an on-site biobank for both therapeutic and diagnostic applications. Professor Gerd Schmitz, the former director of the institute, explained: “We first decided to invest in biobanking about 10 years ago; we were already cryopreserving materials for transfusions and scientific applications, and were getting more and more requests to store residual patient

A customized workdeck allows access to both the automation track and the LiCONiC storage unit

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samples for clinical studies. Instead of developing a separate biobanking facility, we chose to create what we have termed a ‘healthcare-integrated biobank’, with the cryopreservation activities occurring side-by-side with daily testing.”

The institute processes and cryopreserves a wide range of samples – including stem cells, blood/plasma preparations and blood cell isolates – on behalf of the clinical disciplines associated to the University Hospital in Regensburg. As materials from the biobank can be used in both diagnostic research and therapeutic applications, the biobank must adhere to strict clinical and industrial standards, making automation a logical step. Gerd continued: "We needed a highly sophisticated control system, with stringent quality controls, that could be integrated into the laboratory workflow.

This required a sampling workstation that could be connected directly to our existing automated laboratory system, the ADVIA® LabCell Automation Solution from Siemens.

We discussed our needs with both our biobanking collaborators and Siemens, and selected the Freedom EVO 200 workstation as the best fit for our existing set-up.”

“The open architecture of this platform made it very straightforward to develop the sample reformatting and preparation protocols, but we required a custom solution in terms of both the hardware and software to allow it to interface with the Siemens system and our automated biobank project. Based on our requirements, the Tecan Integration Group (TIG) shortened

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The TIG solution needed to integrate with the laboratory’s existing automated track system

the workdeck, allowing the instrument’s four-channel Liquid Handling (LiHa) Arm to pipette samples directly from Vacutainers® on the LabCell’s sample track. The TIG team also integrated a LiCONiC STR44 cooled storage unit below the workdeck – which can be accessed by one of the workstation’s Robotic Manipulator Arms via a cut-out for a ‘periscope’ lift – and an XSD-96 PRO high speed whole rack tube capper (FluidX).”

“The software integration was more complex, as the Freedom EVO needed to interface directly with the hospital LIMS, the LabCell system, the FluidX decapper, the LiCONiC unit and, ultimately, the ASKION C-line® HS200 cryostore. Using Pegasus software, Tecan’s engineers were able to create a bespoke interface enabling the two-way transfer of sample IDs and plate layout data between the various systems, allowing us to not only aliquot samples for cryostorage, but also to produce daughter tubes for offline secondary and specialist testing.”

"Incoming patient samples now undergo routine clinical analysis, then the remainder of each sample is aliquoted by the Freedom EVO platform. Samples are transferred to either 700 μl tubes with 1D barcodes for cryostorage, or 2D-barcoded 1 ml tubes for offline testing according to data from the LIMS systems.

Samples for secondary assays are then manually removed from the dedicated unloading area, while biobank samples are transferred to the LiCONiC storage unit. The entire LiCONiC system can then

simply be wheeled across and docked with the ASKION cryostore. This can be for short-term storage of up to one year for in-house therapeutic regimen testing, medium-term storage of two to five years for clinical trials, or long-term storage for up to 10 years for clinical research studies."

"Before getting the Tecan solution, we were doing all of the aliquoting for biobanking and secondary testing by hand, including carrying trays from the automated store to the workbench and sorting samples manually. Now both the biobank samples and secondary workbench analyses can be pipetted automatically, eliminating erroneous sampling and manual handling errors. We can even create worklists for other laboratories and biobanks, helping

“It was easy to connect the Freedom EVO platform to our other laboratory automation systems.” to improve planning and communication and making the whole process more efficient," Gerd concluded.

To read more about University Hospital Regensberg, go to www.uniklinikum-regensburg.de To learn more about the Tecan Integration Group, visit www.tecan.com/tig

The LiHa Arm can pipette samples directly from tubes on the sample track

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Fingerprinting food Surveillant provides rapid and reliable screening methods to help food and beverage manufacturers monitor their products and raw materials. Using an Infinite® M1000 PRO, the company has developed a simple, low cost method of ‘fingerprinting’ products based on their intrinsic fluorescence, providing a rapid screening technique to help detect counterfeit or adulterated foodstuffs.

Fred Behringer, Surveillant founder

Brand recognition and reputation are important factors in the consumer goods market, particularly for foods and beverages. Ensuring the quality, authenticity and safety of foodstuffs is therefore a constant challenge for producers, with a majority of companies operating extremely stringent quality control and authentication programs to guarantee the quality and provenance of their raw materials and products.

Recognizing that the cost and complexity of this testing can be a significant burden for large-scale QC programs, Connecticut-based Surveillant LLC has developed rapid and economical methods for ‘fingerprinting’ foods and beverages, identifying suspect products for further testing. Surveillant founder Fred Behringer explained: “There are a lot of very effective

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FOOD SCIENCE TECAN JOURNAL 3/2015

techniques for detecting the quality, purity or authenticity of materials, but these standard methods can be relatively expensive, limiting the number of samples that can be tested. Surveillant aims to offer complementary techniques to supplement existing QC workflows, providing methods that are rapid and inexpensive, allowing higher throughput and larger-scale sampling. By using our techniques for front-line testing, only samples that yield ambiguous or suspicious results need further analysis by more expensive and time-consuming techniques – such as GC-MS – reducing the overall cost.”

“We have focused primarily on spectroscopic techniques, as these

generally offer rapid, inexpensive measurements, with fluorescence measurements being the real workhorse.

The idea is to keep things as simple as possible, avoiding the cost and variability associated with complicated chemistries, and so we use the intrinsic fluorescence present in most foods and beverages to create 3D spectral ‘fingerprints’ which can be compared to an in-house database.”

The simplicity and potential economic benefits of this approach have recently been demonstrated, allowing extra virgin olive oil to be distinguished from olive oil and other edible oils1. Fred continued: “The authenticity of extra virgin olive oil is an ongoing concern, with strict production

Surveillant’s label-free technique relies on the Infinite M1000 PRO’s ability to create consistent fluorescence spectra

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The method can be used to discriminate between closely related products, such as extra virgin olive oil (EVOO) and olive oil (OO)

requirements, high consumer demand and occasional poor harvests. The resulting combination of high prices and limited supply makes it a target for adulteration with less expensive oils, and so we have developed a rapid microplate-based method to help identify adulterated extra virgin olive oil. This method requires no sample preparation prior to analysis, and the results can be automatically processed, providing a low cost, effective technique which can be easily implemented at multiple sites.”

“The sensitivity of the fluorescence reader is obviously crucial for this approach, as is the ability to freely select the most appropriate excitation and emission wavelengths for each target product. When I began developing the method in 2007, I compared monochromator-based microplate readers from different manufacturers head-to-head for several months, looking for the ability to create consistent spectra and discriminate between closely related products along with ease of use. The Tecan offering – at the time it was the Sapphire2™ – offered the best performance in my hands, and I have been very happy with my decision.

In 2013 I upgraded to the Infinite M1000 PRO. Tecan’s instruments have been reliable and robust – we have successfully shipped them to other countries for use in remote labs on several occasions, where they have performed well.”

“The results can be automatically processed, providing a low cost, effective technique which can be easily implemented at multiple sites.”

“Tecan’s software is another strong point. i-control™ is easy to use and allows you to export data directly to an Excel® spreadsheet. This is a particularly useful feature for our work, as the spectral reconstruction and multivariate analyses we perform are quite different from the standard techniques used in biochemical assays, so being able to access the raw data easily is a real bonus.”

1) Behringer, F. Rapid Evaluation of Extra Virgin Olive Oil Using Fluorescence Spectra. Spectroscopy:

The Application Notebook, Sept 2015.

To find out more about Tecan’s Infinite M1000 PRO, visit www.tecan.com/ infinitem1000 To learn more about Surveillant, go to www.surveillanttech.com

FOOD SCIENCE TECAN JOURNAL 3/2015

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Off-the-shelf NGS library prep for Ion Torrent™ sequencing The Leiden University Medical Center has integrated the Freedom EVO® NGS workstation into its molecular diagnostic testing and clinical research workflows. Taking advantage of this preconfigured solution, the center was quickly able to commission the platform for routine testing, while still having the flexibility to develop new protocols and conduct research studies.

Leiden University Medical Center (LUMC) is a modern university hospital combining cutting-edge patient care with a strong clinical research program. The hospital’s Department of Pathology offers a full range of diagnostic services for medical and surgical patients – both in house and for national and international referrals – as well as undertaking a variety of clinicallyfocused research projects. Dr Ronald van Eijk, a researcher in the department, explained the role new technologies play: “Our department is always looking at new ways of meeting the clinical needs of our patients, including developing research technologies for clinical applications.

Molecular diagnostics is a good example of this, and the field has come a long way since the department first began applying molecular biology techniques in the 1990s.

There is now a huge clinical demand for molecular diagnostic testing and, of course, there are a wide range of standard methods and diagnostic kits on the market, but the technology also continues to evolve on the research side, so we are always looking at new techniques.”

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GENOMICS TECAN JOURNAL 3/2015

“We began investigating the clinical applications of next generation sequencing (NGS) about three years ago, and have been offering clinical screening of various cancer genes since the beginning of the year using the Ion AmpliSeq™ Cancer Hotspot Panel (Life Technologies). Although we do not have any NGS platforms within the department, we have access to a variety of sequencers, including Ion PGM™ and Ion Proton™ systems (Life Technologies), and MiSeq™, HiSeq™ and NextSeq™ 500 platforms (Illumina).”

“Sample preparation is critical to the reliability of any diagnostic test, and is especially important for NGS protocols.

Despite not being a particularly high throughput lab, we try to automate as much of our workflow as possible, helping to maintain the high quality standards necessary in a clinical environment. We have been using Tecan workstations for almost 10 years now, and already had a Tecan liquid handling workstation for pre-PCR sample processing, so were keen to see what the company could offer us

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The platform is preconfigured to allow complete automation of library preparation for various NGS chemistries

Setting up the Freedom EVO NGS workstation is quick and easy, saving valuable operator time

in terms of post-PCR library preparation.

The Freedom EVO NGS workstation had just been launched and fitted our needs perfectly, as the entire Ion AmpliSeq library preparation protocol was already pre-installed on the system. This allowed us to implement the system for routine diagnostics within just two months of getting the platform up and running.”

“It is very easy to develop new protocols on the workstation, which is important for both method development and the implementation of new standard diagnostic kits. Our previous experience with Tecan platforms meant that our staff were already very comfortable developing new methods or editing protocols using the standard Freedom EVOware® software, but it is also very intuitive for new users; over the course of a three-month placement, a trainee from the nearby University of Applied Sciences Leiden was able to develop several new protocols with limited supervision.”

“We currently process between 30 and 50 patient samples every week for routine molecular diagnostics, and the system is very easy to use via the TouchTools™ touchscreen interface. At the moment we have only implemented the most timeconsuming and laborious elements of our workflow, but it is already saving us almost two hours of technician time per run. We plan to bring the last portion of the Ion AmpliSeq protocol into routine use very soon – saving us even more time – as well as continuing with the implementation of other technologies and assay kits.”

“Alongside our routine testing, we have a large number of research projects which use the platform for library preparation.

These studies can vary in size from under 100 to over 1,000 samples, so the instrument’s 96-well plate format and throughput are invaluable, saving a lot

Disposable tips ensure sample security and prevent cross-contamination

“The entire Ion AmpliSeq library preparation protocol was already pre-installed... allowing us to implement the system for routine diagnostics within just two months.” of time and providing the additional capacity we need to run research projects alongside our clinical workload.”

To learn more about the Leiden University Medical Center, go to www.lumc.nl To find out more about Tecan’s Freedom EVO® NGS workstation, visit www.tecan.com/ngs

GENOMICS TECAN JOURNAL 3/2015

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Designer proteins Researchers at the University of Montreal have benefitted from Tecan’s collaboration with SciRobotics to automate DNA assembly protocols for synthetic biology. Combining a Freedom EVO® 200 with a Pickolo™ Colony-Picker and various other components, the Systems Biology and Synthetic Biology Research Unit has built a streamlined cloning workflow with increased throughput and reliability.

Synthetic biology blends molecular and systems biology with computer-based modeling and new genetic engineering methods. Part of the University of Montreal’s Institute for Research in Immunology and Cancer, the Systems Biology and Synthetic Biology Research Unit – led by Professor Michael Tyers – uses systems-level interrogation of complex cellular networks to build models of cellular behavior. These models are then tested through synthetic biology approaches, allowing the team to both re-engineer natural pathways and build artificial networks that can perform novel biological functions. Almer van der Sloot, Senior Research Associate in the unit, explained: “Broadly speaking, we design and develop artificial signaling circuits and sensors, investigating how yeast and mammalian cells respond to these signals using primarily proteinbased synthetic biology approaches.

By combining DNA elements encoding different functionalities, we can create

Importantly, the platform also has an

“Thanks to the scalability it offers, we can now ‘think bigger’ when designing our experiments.”

new molecular circuits and study their effects on cells, with a view to potential applications in biomedicine and drug discovery.”

Raik Grünberg, a former Senior Research Associate in the lab, continued: “To meet these aims, we decided to implement an automated and comprehensive cloning and DNA assembly workflow on our Freedom EVO 200 workstation. Our workflow starts with manual or semiautomated design of DNA constructs and assembly primers. We then perform PCR amplification and clean-up of the template constructs, followed by Gibson

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CELL BIOLOGY TECAN JOURNAL 3/2015

Isothermal Assembly and transformation into E. coli cells. The transformed bacteria are then plated out onto agar in either 6- or 12-well plates for incubation. After the incubation, we pick and screen the colonies to verify correct assembly.”

The unit’s Freedom EVO workstation is configured with an eight-channel Air LiHa Arm, a RoMa Arm, two BioShake® 3000 plate shakers (Q.Instruments), a barcode reader, a Te-VacS™ vacuum separator and EchoTherm™ RIC20 Series heating/ cooling units (Torrey Pines Scientific).

integrated Pickolo Colony-Picker from SciRobotics. Raik continued: “Automating colony picking was critical, eliminating the need for someone to sit down and pick all those colonies by hand. The Pickolo provides a cost-effective and space-saving solution, and proved easy to integrate into our workflow. The preparation of so many agar plates turned out to be the next bottleneck, so we automated this as well.

This not only speeds up plate production, it is also far more reproducible than manual procedures, ensuring that each one is reliably filled to the specified volume.”

Plating out bacteria onto the agar plates is another important step which has traditionally been difficult to automate.

The Freedom EVO’s Air LiHa Arm has been programmed to pipette in a spiral

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Integration of the Pickolo and other third-party devices onto the workstation proved key to automating the DNA assembly workflow

pattern across the surface of the agar

manually. Importantly, automation of our

in each well of the plate, spreading the

cloning and DNA assembly workflow has

bacterial cells over a large area. The

improved accuracy and reproducibility, as

team has also developed a second plate

the Freedom EVO workstation’s advanced

streaking strategy using SLAS-format

liquid handling capabilities eliminate

8-channel reservoir plates filled with

pipetting or sampling mistakes.”

agar. The E. coli culture is pipetted into one end of the channel by the Air LiHa,

“The Tecan team integrated all the third-

then the plate is lifted at one end by the

party components on the Freedom EVO

RoMa Arm. The liquid simply flows down

workstation, as well as dealing with our

the channel, giving a good spread of

complicated and diverse questions during

bacterial cells on the agar surface. This

the build. Most of the workflow

is technically simpler, offering a higher

automation was actually performed

throughput, but reduces the definition of

together with Xingjian Xu, an internship

individual colonies at higher cell densities

student who joined the lab for one year via

compared with spiral plating. “Overall,

the UBC Vancouver co-op program, and an

automation has given us a dramatically

application expert from Tecan also visited

higher throughput,” Almer added. “We can

us twice to help us learn more about the

now routinely perform 48 or even 96 DNA

Freedom EVO’s capabilities. Thanks to the

assembly reactions from start to finish in

scalability it offers, we can now ‘think

the time it used to take us to do about 12

bigger’ when designing our experiments.

Almer van der Sloot and Raik Grünberg

We also plan to automate protein interaction studies on this system, and have already begun integration of a ForteBio Octet® system onto the Freedom EVO for this application. Once complete, this will give us the ability to go straight from cloning to protein interaction measurements on the one platform,” Raik concluded.

To learn more about Tecan’s synthetic biology solutions, visit www.tecan.com/syntheticbiology To read more about the Systems Biology and Synthetic Biology Research Unit, go to www.iric.ca/en/research/principalinvestigators/michael-tyers

The Freedom EVO is also used to generate consistently filled agar plates

CELL BIOLOGY TECAN JOURNAL 3/2015

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A personal touch for wine microbiology The Wine Microbiology and Microbial Biotechnology Laboratory at the University of Adelaide has developed a customized solution offering fully automated sampling for yeast fermentations.

Based on a Freedom EVO® 200 platform, this system frees researchers from the need to manually aliquot samples day and night for up to three weeks.

hundreds or even thousands of strains, often from heterogeneous populations.

Monitoring the fermentation process for large numbers of samples is also very laborious, requiring regular sampling of fermentation vessels every six, four, or even two hours over the course of several days to several weeks.”

Members of the Wine Microbiology and Microbial Biotechnology Laboratory team with the customized Freedom EVO

The Wine Microbiology and Microbial Biotechnology Laboratory is part of the University of Adelaide and the Wine Innovation Cluster. Led by Professor Vladimir Jiranek and Associate Professor Paul Grbin, the group aims to improve the winemaking process by developing new yeast strains offering characteristics such as faster fermentation rates, higher tolerance to ethanol and improved nutrient utilization. Dr Tommaso Liccioli, a postdoctoral research fellow in the laboratory, explained: “Winemaking is a complex process, with grape juice undergoing many biochemical and chemical reactions to become wine.

These processes are largely carried out by yeast and bacteria, which have been ‘domesticated’ for thousands of years to withstand the harsh conditions during fermentation and impart specific

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MICROBIOLOGY TECAN JOURNAL 3/2015

characteristics to the finished product.

However, new wine styles, modern viticulture techniques and the effect of climate change are pushing fermentation conditions to extreme levels, challenging the fitness of these micro-organisms. This can result in problems during fermentation, leading to undesirable wine characteristics and financial losses for the industry.”

“Our aim is to develop novel yeast and bacteria strains which improve the winemaking process. However, because the use of genetic engineering techniques is prohibited in the food and beverage industry in most global markets, we focus on more traditional approaches, such as directed evolution and mutagenesis.

These methods can be equally effective, but are often very time consuming, requiring large-scale screening of

“An important part of our job is to modernize these classical microbiological techniques and develop powerful new approaches for microbial improvement.

We already had a number of robotic processing systems in the lab, as well as the necessary programming and engineering expertise in house, and so we were interested in developing a system that would allow fully automated screening. We looked at the various liquid handling platforms on the market, and Tecan’s Freedom EVO really stood out, enabling us to build a walkaway fermentation monitoring solution that would generate 96-well microplates ready for loading onto our various analytical instruments. The real strength of the Tecan system was its flexibility – including the software – which allowed us to integrate our own custom hardware solutions onto the platform with relative ease.”

“Our first task was to create a jacketed carrier system allowing 96 fermentations to run simultaneously on the Freedom EVO’s workdeck. We developed four 24-position jacketed carriers which have warm water pumped through them to maintain the optimal fermentation temperature, and each carrier has a 24-position stirrer underneath to continuously mix the fermentations. Each flask has also been

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fitted with a custom-designed airlock along with a silicon septum in the top, allowing the workstation’s Liquid Handling (LiHa) Arm to sample the anaerobic fermentations using fixed tips. At userdefined intervals, aliquots are transferred directly from the flasks to purpose-built cooled microplate carriers which maintain the samples at ­10 oC until the user is ready to remove them from the workstation for analysis. It only takes half a day to set up a 96-fermentation experiment, then you can just remotely monitor its progress via a smartphone from another lab, from home or – because this is Australia – from the beach. Compared to having to be in the lab every few hours, day and night, this is fantastic. Everyone here loves the system, and is using it a lot.”

“Although we had previous experience with Tecan’s equipment and services – we already had an Infinite® M200 microplate reader in the lab – we had no real way of knowing if this system was going to work, as we weren’t aware of anyone that had tried anything similar. However, the Tecan team here in Australia was extremely good. Their communication was great, and they helped us with protocol development

The LiHa Arm’s fixed tips allow direct transfer of samples from fermentation flasks…

and script writing. The platform’s technical specifications were also very thorough in terms of exactly what the instrument could do, what pressures could be applied to the LiHa tips, etc., so we were fairly confident. Once we had designed and built our bespoke hardware and put everything together, it worked incredibly well first time. We got extremely good results straight away and, after a bit of fine tuning, we’re very happy with the system.”

“At the moment, samples are still analyzed offline, but the next step is to develop a system that monitors at least a few key metabolites – such as sugar and alcohol concentrations – during the fermentation.

One option is to integrate a small, benchtop NMR system underneath the workdeck of the Freedom EVO, and we are already discussing this with an instrument manufacturer in New Zealand. We could then run the NMR analyses in virtually real time, and still collect an aliquot of each sample in microplates to perform offline assays. It would also be good to replicate our set-up in other labs in Australia or further afield, allowing direct comparison of results between platforms.”

“You can just remotely monitor its progress via a smartphone from another lab, from home or – because this is Australia – from the beach."

To find out more about Tecan’s food sciences solutions, visit www.tecan.com/food To learn more about the Wine Microbiology and Microbial Biotechnology Laboratory, go to www.agwine.adelaide.edu.au/winemicro

…to cooled microplates, ready for offline analysis

MICROBIOLOGY TECAN JOURNAL 3/2015

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Accelerating results from bench to bedside The direct digital dispensing capabilities of the HP D300 are helping to identify potential new treatments for acute lymphoblastic leukemia at University Children’s Hospital Zurich. By enabling picoliter drug volumes to be dispensed straight into cell-based assay plates, the system is helping researchers to rapidly test novel drug combinations directly in patient-derived leukemia cells.

The Division of Pediatric Oncology at University Children’s Hospital Zurich (Kinderspital Zürich), Switzerland, has an active translational research program, working in close collaboration with the University of Zurich and other institutes to identify potential new treatments for a number of childhood cancers. As the most frequent form of childhood leukemia, acute lymphoblastic leukemia (ALL) is a key area of research, and the hospital has a special interest in drug-resistant ALL, using a combination of cell-based assays and mouse models to identify novel therapeutic strategies. Dr Jean-Pierre Bourquin, Associate Medical Director of Oncology at the hospital, explained: “We have built a model system that allows us to test material from selected clinicallyrelevant patients against new drugs and drug combinations. We use a mouse xenograft technique – implanting patientderived leukemia cells into a tolerant mouse system – to both generate cells for microplate-based co-culture assays and to provide an in vivo model. This approach ensures we have enough material to do large-scale investigations which are directly relevant to our patients.”

“Due to the drug-resistant nature of the ALL samples we use, we do a lot of drug combination studies, and perform all our cell-based assays in 384-well plates.

Designing and pipetting these studies in such high density formats manually can be very time consuming and, like any manual activity, can be prone to errors and inter-operator variability, and so we were looking for ways to improve and streamline our workflow. Automation was an obvious option but, because we are only a small satellite laboratory without the resources and support of a major university facility, a large liquid handling workstation was not a viable option. We discussed our needs with our local Tecan representative, who suggested the HP D300 Digital Dispenser.

This instrument is ideal for us; it doesn’t take up much space, it’s cost effective, and it’s very easy to use.”

“The D300 is also very convenient for our drug combination studies, allowing us to rapidly design and plan experiments simply by entering the relevant parameters into a matrix. The system then randomizes the plate layout and dispenses the correct volumes of each compound directly into the microplate wells. It’s incredibly fast and so simple; what would take half an hour by hand is done in just a few minutes. This is a huge advantage when handling humanderived cells, as they spend as little time as possible outside of the incubator.”

are currently exploring using it for drug activity profiling as part of a clinical trial for pediatric patients whose leukemias do not respond to the standard treatments. These patients are offered highly accelerated whole genome investigations and, at the same time, we profile the activity of a selection of compounds for compassionate use ‘salvage’ treatments. In this situation, the speed and reproducibility offered by the D300 is obviously a real benefit.”

“For example, in a recently published study1, we used this approach to help us investigate the drug susceptibility of a very rare TCF3-HLF-positive ALL characterized by a chromosomal translocation. Using the D300, we were able to investigate the sensitivity of this ALL to venetoclax – a drug more commonly used in chronic leukemias – in combination with a range of other therapeutics. The data from this study was very promising, and we are now investigating these combinations using the in vivo mouse model, with outstanding results.”

“The speed of the instrument is also of potential clinical importance, as we

Viktoras Frismantas and Dr Scott McComb with the hospital’s D300 instrument

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DRUG DISCOVERY TECAN JOURNAL 3/2015

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“The introduction of the D300 has been a big improvement for our workflow, proving the ideal complement to the equipment we already had in the lab. It has enabled us to substantially accelerate many experiments, exploring more complex drug combinations and asking more focused questions. We mostly work with small molecules in DMSO, but the recent upgrades to the D300 mean that we now also have the ability to dispense aqueous solutions, allowing us to investigate biological agents, such as antibodies and antibody-derived therapeutics. Ultimately, the system is helping us to take a more personalized approach to the management of this rare population of patients with highly resistant disease.”

“This instrument is ideal for us; it doesn’t take up much space, it’s cost effective, and it’s very easy to use.”

To find out more about Tecan’s D300e, visit www.tecan.com/d300e To learn more about University Children’s Hospital Zurich, go to www.kispi.uzh.ch 1) Fischer, U et al. Genomics and drug profiling of fatal TCF3-HLF−positive acute lymphoblastic leukemia identifies recurrent mutation patterns and therapeutic options. Nature Genetics, 2015, 47, 1020-1029.

DRUG DISCOVERY TECAN JOURNAL 3/2015

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Human genetics – mapping the future of medicine

Human genetics and drug discovery are now inextricably linked, with large pharmaceutical companies, small biotech and even academic laboratories turning to sequencing data to identify potential targets for new therapies. But is this information being used to the best effect? And does genetic testing have a role to play in helping today's patients as well as tomorrow’s? Dr Pierre-Alain Menoud, Scientific Manager for Molecular Diagnostics at Unilabs in Lausanne, Switzerland, discusses the potential benefits of genetic testing for both the understanding and treatment of disease.

When I started in molecular diagnostics in

of adverse side effects and diversity of

2002, oncogenetics was still in its early days,

disease types, has made this type of genetic

with very few tests available. Despite this,

susceptibility testing (companion diagnostics)

there was huge interest in the potential of

standard practice prior to commencing

genetic testing for the diagnosis of various

therapy for many cancers. Unfortunately, the

cancers – such as chronic myelogenous

use of pharmacogenetics is still relatively

leukemia, prostate and lung cancers – and

rare outside of oncology, despite the huge

the field quickly evolved in terms of both

potential economic and patient benefits. The

diagnostic testing and pharmacogenetics.

reasons for this are complex, but essentially

The sequencing of the human genome or

come down to a combination of two factors:

genes related to cancers has undoubtedly

the relatively low cost of other therapeutics

led to a number of breakthroughs in the

compared with chemotherapy agents, and a

understanding and diagnosis of numerous

lack of understanding of the potential patient

cancers but, more importantly, continues to

benefits among physicians.

provide potential therapeutic targets and treatment strategies.

One field which is just beginning to explore pharmacogenetics as a way of improving

Dr Pierre-Alain Menoud, Scientific Manager for Molecular Diagnostics at Unilabs

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GENOMICS TECAN JOURNAL 3/2015

The success of pharmacogenetics approaches

treatment is psychiatry. Many patients in this

in oncology is well documented – the

field receive long-term treatment in the form

most famous example being the detection

of antidepressants or antipsychotics, yet a

of HER2 over-expression for treatment

large proportion respond poorly to treatment,

with monoclonal antibody trastuzumab

either in terms of low efficacy or adverse side-

(Herceptin®) – with a huge potential market

effects. These issues can significantly impact

around the world. The high cost of most

on the patient’s general health – leading

cancer therapies, combined with the range

to escalation of their condition, metabolic

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complications or other, indirectly-related

for large, centralized facilities such as Unilabs

sequencing chemistries and assay

health problems – meaning there are large

– no one center can maintain comprehensive

technologies. NGS is just beginning to

potential health and economic benefits to

knowledge of every genetic abnormality.

benefit from this approach, with automated

improving treatment strategies. As the cost of

Instead, laboratories need easy access to

library preparation now available, but even

genetic testing continues to fall, both health

sequencing data, current understanding and

more needs to be done to provide user-oriented

insurance companies and healthcare providers

prescribing practices from across the globe,

solutions that minimize turnaround times for

are increasingly looking to pharmacogenetics

to aid physicians and, ultimately, improve

analysis and the risk of human errors.

to help individual patients, with many genetics

patient care. This is where the molecular

laboratories reporting very high success rates

diagnostics industry has a role to play. To fully

for improving prescribing practices and patient

benefit from the information that genetic

outcomes for psychiatry.

testing – and particularly next generation sequencing – can provide, we need to develop

Since the Human Genome Project first

systems that offer full data interpretation;

reported the complete mapping of the human

taking the raw data from sequencers,

genome in 2003, the general public has also

automatically processing and analyzing it,

become far more aware of genetic testing. In

then searching relevant databases to identify

addition to the benefits offered by companion

specific mutations, related scientific papers

diagnostics, many patients are now looking for

and even treatment strategies. This would not

genetic 'explanations' of congenital disease,

only provide physicians with the information

even those which do not yet have any known

required to act on the results they receive, but

treatment strategies. Similarly, physicians are

would also free up resources for more clinical

increasingly finding themselves relying on

research – further improving patient care

specialist molecular diagnostics facilities to

in the long term.

“We need complete solutions that are reliable and easy to use.”

provide insight into individual cases across a broad range of disciplines, helping to identify

At the other end of the spectrum, the ever-

relevant genetic tests for everything from

increasing demand for testing means that

coagulation and anesthesia for surgical

sample numbers will continue to rise steadily

procedures to prenatal genetics and

for molecular diagnostics laboratories

medically-assisted procreation.

around the globe. This requires high throughput, reliable automation of pre-

The diverse range of medical specialties

analytical sample processing and set-up.

now served by genetic testing laboratories

While the liquid handling technologies

means that individual centers can no longer

required for this already exist, we need

support the required level of expertise across

complete solutions that are reliable and

every field. While each laboratory can provide

easy to use, while still providing the

expertise in one or two disease areas – more

flexibility necessary to work with various

GENOMICS TECAN JOURNAL 3/2015

27

TJ Meet Tecan at these events Americas BioProcess International Conference & Exhibition

Boston, USA

26 – 29 Oct 2015

AMP Association for Molecular Pathology 2015 Annual Meeting

Austin, USA

05 – 07 Nov 2015

ASCB 2015 American Society for Cell Biology Annual Meeting

San Diego, USA

12 – 16 Dec 2015

SLAS Society for Laboratory Automation & Screening 2016

San Diego, USA

23 – 27 Jan 2016

The 16th Beijing Conference and Exhibition on Instrumental Analysis

Beijing, China

27 – 30 Oct 2015

JSSX 30 Annual Meeting of The Japanese Society for the Study of Xenobiotics

Tokyo, Japan

12 – 14 Nov 2015

Asia and Pacific th

ASI 45 Annual Scientific Meeting of the Australasian Society for Immunology

Canberra, Australia

29 Nov – 03 Dec 2015

BMB Biochemistry and Molecular Biology 2015

Kobe, Japan

01 – 04 Dec 2015

MEDICA 2015

Düsseldorf, Germany

16 – 19 Nov 2015

4 National Biobank Symposium 2015

Berlin, Germany

09 – 10 Dec 2015

Arab Health 2016

Dubai, United Arab Emirates

25 – 28 Jan 2016

th

Europe, Middle East and Africa th

Tecan is a pioneer of innovative solutions for life sciences and clinical diagnostics. For 35 years, we have supported our customers in helping to make the world a healthier and safer place.

Headquarters: Tecan Group Ltd., Seestrasse 103, CH-8708 Männedorf, Switzerland T +41 44 922 8111 F +41 44 922 8112 info@tecan.com

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www.tecan.com

Tecan Journal, Customer Magazine of Tecan Trading AG., ISSN 1660-5276 Design: OTM/London www.otmcreate.com Photography: Günter Bolzern/Zürich www.bolzern.tv Editor in Chief: Tecan Trading AG, Antonietta Allocca Editor: kdm/UK www.kdm-communications.com Print: DAZ Druckerei Albisrieden AG/Zurich www.daz.ch Address: Tecan Trading AG, Marketing Communications, Seestrasse 103, CH-8708 Männedorf, Switzerland, journal@tecan.com, www.tecan.com To register for the Tecan Journal please go to www.tecan.com/journal © 2015 Tecan Trading AG, Switzerland, all rights reserved.

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EVENTS TECAN JOURNAL 3/2015

Tecan Group Ltd. makes every effort to include accurate and up-to-date information within this publication, however, it is possible that omissions or errors might have occurred. Tecan Group Ltd. cannot, therefore, make any representations or warranties, expressed or implied, as to the accuracy or completeness of the information provided in this publication. Changes in this publication can be made at any time without notice. All mentioned trademarks are protected by law. In general, the trademarks and designs referenced herein are trademarks, or registered trademarks, of Tecan Group Ltd., Mannedorf, Switzerland. A complete list may be found at www.tecan.com/trademarks.

Product names and company names that are not contained in the list but are noted herein may be the trademarks of their respective owners. For technical details and detailed procedures of the specifications provided in this document please contact your Tecan representative.

This journal may contain reference to applications and products which are not available in all markets. Please check with your local sales representative: www.tecan.com/contact